3.1Background: Overall Approach to Patient Care

In the era of increased demand on the time per patient for rheumatologists, SS patients represent the proverbial patient with a long list of questions regarding problems of topical therapy of dry eyes and mouth, most of which are not immediately life threatening. In addition to the limited time available, there is only a limited amount of information that a patient can retain during their visit.

3.1.1Pearl

Use the Internet as a means to instruct the patient and help them become actively involved in the therapeutic process. Chapter 4 will contain a series of tables regarding choice of artiÞcial tears, saliva, and topical therapy that will be included in the ÒStandards of CareÓ guidelines that are currently being formulated.

We have found that many of our patients have Internet addresses (or that their children or family members have computers). For those without computers, the local library offers access to the Internet, and instructions about simple Internet use are generally available there. Thus, during our patient visits, we attempt to provide the patient with a general overview of the treatment plan and then email them an ÒattachmentÓ with more speciÞc written instructions as needed.

Patients increasingly want to be an active partner in the treatment plan and we encourage this. However, we also warn them that the Internet can be a citadel of misinformation.

3.1.2Pearl

A helpful hint (humorously referred to as a Òpearl of wisdomÓ) for the rheumatologist is to instruct patients to restrict their Internet medical information searches to a much more reliable (albeit less well-known) search engine such as “Google Scholar” (http://www.googlescholar.com).

The patient can be directed to the Internet to read available patient information on validated websites such as

¥http://www.WebMD.com

¥http://www.MedScape.com

¥http://www.eMedicine.com

¥http://www.sjogrens.org

3.2Diagnosis Criteria and Laboratory Tests

3.2.1 Myth

There is now a validated diagnostic criteria structure for Sjögren’s syndrome that has been adopted by the American College of Rheumatology (ACR).

Fact: Although rheumatologists are using the EuropeanÐUS consensus criteria described by Vitali et al. [1, 2], the ACR has not yet accepted these criteria. Although the criteria have been validated in a European cohort, it has not been systematically studied in any US cohort. The European criteria are listed in Table 3.1. An example of a salivary gland biopsy from an SS patient, characterized by focal lymphocytic inÞltrates, is shown in Fig. 3.1.

Table 3.1 Consensus criteria for the diagnosis of primary and secondary SjšgrenÕs syndrome. The diagnosis requires either a positive antibody to SS-A/SS-B or a

characteristic minor salivary gland biopsy. Revised classiÞcation criteria for SjšgrenÕs syndrome

Fig. 3.1 Minor salivary gland biopsies. a Biopsy from a SjšgrenÕs patient where clusters of lymphocytes (termed foci) can be seen. Arrows also denote regions of the glandular lobule where the acini and ducts remain intact but

non-functioning. b Biopsy from a patient with symptoms of a dry burning mouth but that lacks focal lymphocytic inÞltrates

3.2.2 Pearl

There are recent criteria for disease activity and disease damage indices.

Comments: The same EEC consortium (Vitali et al. (Vitali, 2007 #16385)) that spearheaded the new consensus criteria has recently presented an activity and disease damage index (Tables 3.1 and 3.2) that will serve as a starting point for a uniform database basis for clinical data collection and research studies. These indices will provide the same type of standardization that the ACR criteria provided for RA.

3.2.3 Myth

The antinuclear antibody (ANA) and antiSjögren’s SS-A (Ro) antibody are specific for primary Sjögren’s syndrome.

Comments: Patients commonly arrive in the rheumatologistÕs ofÞce after the primary care physician has ordered a battery of tests for vague symptoms and a positive ANA and/or a positive anti-SS-A (Ro) emerged.

ANA assays can be useful in recognizing certain disease conditions but can create misunderstanding when the limitations are not fully appreciated. The ANA has a higher sensitivity than speciÞcity. Tan et al. [3] measured the range of antinuclear antibodies (ANAs) in ÒhealthyÓ individuals.

¥Fifteen international laboratories experienced in performing tests for ANA by indirect immunoßuorescence participated in analyzing coded sera from healthy individuals.

¥Except for the stipulation that HEp-2 cells should be used as substrate, each laboratory used its own in-house methodology so that the data might be expected to reßect the output of a cross-section of worldwide ANA reference laboratories.

¥The sera were analyzed at four dilutions: 1:40, 1:80, 1:160, and 1:320.

¥They found that in healthy individuals, the frequency of ANA did not differ signiÞcantly across the four age subgroups spanning 20Ð60 years of age.

¥This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320.

An interesting Þnding of this study was a remarkably higher incidence of ÒfalseÓ-positive ANAs in patients with either a monoclonal gammopathy or a myelodysplastic syndrome; this observation was attributed to the association of autoantibody with a ÒdysregulatedÓ immune system at the bone marrow level.

The same consortia of research labs (led by Tan et al. (Tan, 1997 #6375; Tan, 1996 #5941; Tan, 1999 #99186629; Tan, 1973 #354)) also studied ELISA detection methods using normal and patent sera.

¥Precision, based on evaluation of replicate samples, varied from very good to poor for particular antigens [4Ð6].

Lightfoot has used Bayesian calculation to determine that an individual with an ANA of 1:320 (and lacking other clinical criteria to suggest either SS or SLE) has less than a 1:100 chance in developing SLE or SS during a 5-year follow-up interval.

In a more recent analysis, Lopez-Hoyos et al. [5Ð7] conÞrmed the complexity in the clinical laboratory of standardizing ANA testing. ANA testing by indirect immunoßuorescence (IIF) assays is not an automated laboratory test. Efforts are being made to develop easy and semi or automated methods to screen for ANAs using microchip-binding technology. However, the afÞnity columns used to prepare the chips will be Òas good asÓ the sera that are deÞned as deÞnite SSÑand previously we have noted the problems in diagnosis. Similarly, the ÒpositiveÓ sera that go with each assay kit will need to be carefully chosen for their sensitivity and speciÞcity.

3.2.4 Myth